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Science 19 January 1996:
Vol. 271. no. 5247, pp. 363 - 366
DOI: 10.1126/science.271.5247.363
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Reports

Role of -Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor Internalization

Stephen S. G. Ferguson,  William E. Downey III,  Anne-Marie Colapietro,  Larry S. Barak,  Luc Ménard,  Marc G. Caron (1)

beta-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) and contribute to the desensitization of GPCRs by uncoupling the signal transduction process. Resensitization of GPCR responsiveness involves agonist-mediated receptor sequestration. Overexpression of beta-arrestins in human embryonic kidney cells rescued the sequestration of beta2-adrenergic receptor (beta2AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of beta-adrenergic receptor kinase 1. Wild-type beta2AR sequestration was inhibited by the overexpression of two beta-arrestin mutants. These findings suggest that beta-arrestins play an integral role in GPCR internalization and thus serve a dual role in the regulation of GPCR function.


Howard Hughes Medical Institute Laboratories and Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710, USA.
(1) To whom correspondence should be addressed.


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Parathyroid Hormone Receptor Recycling: Role of Receptor Dephosphorylation and {beta}-Arrestin.
S. Chauvin, M. Bencsik, T. Bambino, and R. A. Nissenson (2002)
Mol. Endocrinol. 16, 2720-2732
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Phosphorylation-Independent Desensitization of G Protein-Coupled Receptors?.
C. S. Pao and J. L. Benovic (2002)
Sci. STKE 2002, pe42
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Insulin Induces Heterologous Desensitization of G Protein-Coupled Receptor and Insulin-Like Growth Factor I Signaling by Downregulating {beta}-Arrestin-1.
S. Dalle, T. Imamura, D. W. Rose, D. S. Worrall, S. Ugi, C. J. Hupfeld, and J. M. Olefsky (2002)
Mol. Cell. Biol. 22, 6272-6285
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Transfer of M2 Muscarinic Acetylcholine Receptors to Clathrin-derived Early Endosomes following Clathrin-independent Endocytosis.
K. A. Delaney, M. M. Murph, L. M. Brown, and H. Radhakrishna (2002)
J. Biol. Chem. 277, 33439-33446
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Differential Roles of Arrestin-2 Interaction with Clathrin and Adaptor Protein 2 in G Protein-coupled Receptor Trafficking.
Y.-M. Kim and J. L. Benovic (2002)
J. Biol. Chem. 277, 30760-30768
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Phosphoinositide 3-kinase regulates {beta}2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/{beta}-arrestin complex.
S. V. Naga Prasad, S. A. Laporte, D. Chamberlain, M. G. Caron, L. Barak, and H. A. Rockman (2002)
J. Cell Biol. 158, 563-575
   Abstract »    Full Text »    PDF »
Book Review: Arrestin: Roles in the Life and Death of Retinal Neurons.
P. J. Dolph (2002)
Neuroscientist 8, 347-355
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Oxidative Stress Decreases G Protein-Coupled Receptor Kinase 2 in Lymphocytes via a Calpain-Dependent Mechanism.
M. S. Lombardi, A. Kavelaars, P. Penela, E. J. Scholtens, M. Roccio, R. E. Schmidt, M. Schedlowski, F. Mayor Jr., and C. J. Heijnen (2002)
Mol. Pharmacol. 62, 379-388
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Vasoactive Intestinal Polypeptide Type-1 Receptor Regulation. DESENSITIZATION, PHOSPHORYLATION, AND SEQUESTRATION.
M. A. Shetzline, J. K. L. Walker, K. J. Valenzano, and R. T. Premont (2002)
J. Biol. Chem. 277, 25519-25526
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N-Glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization.
T. KOHNO, A. WADA, and Y. IGARASHI (2002)
FASEB J 16, 983-992
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NK1 Receptor Fused to beta -Arrestin Displays a Single-Component, High-Affinity Molecular Phenotype.
L. Martini, H. Hastrup, B. Holst, A. Fraile-Ramos, M. Marsh, and T. W. Schwartz (2002)
Mol. Pharmacol. 62, 30-37
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Defective lymphocyte chemotaxis in beta -arrestin2- and GRK6-deficient mice.
A. M. Fong, R. T. Premont, R. M. Richardson, Y.-R. A. Yu, R. J. Lefkowitz, and D. D. Patel (2002)
PNAS 99, 7478-7483
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alpha -Thrombin Induces Rapid and Sustained Akt Phosphorylation by beta -Arrestin1-dependent and -independent Mechanisms, and Only the Sustained Akt Phosphorylation Is Essential for G1 Phase Progression.
R. Goel, P. J. Phillips-Mason, D. M. Raben, and J. J. Baldassare (2002)
J. Biol. Chem. 277, 18640-18648
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beta -Arrestin/AP-2 Interaction in G Protein-coupled Receptor Internalization. IDENTIFICATION OF A beta -ARRESTIN BINDING SITE IN beta 2-ADAPTIN.
S. A. Laporte, W. E. Miller, K.-M. Kim, and M. G. Caron (2002)
J. Biol. Chem. 277, 9247-9254
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Heterologous regulation of trafficking and signaling of G protein-coupled receptors: beta -Arrestin-dependent interactions between neurokinin receptors.
F. Schmidlin, O. Dery, N. W. Bunnett, and E. F. Grady (2002)
PNAS 99, 3324-3329
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Independence of Angiotensin II-Induced MAP Kinase Activation from Angiotensin Type 1 Receptor Internalization in Clone 9 Hepatocytes.
B. H. Shah, J. Alberto Olivares-Reyes, A. Yesilkaya, and K. J. Catt (2002)
Mol. Endocrinol. 16, 610-620
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Desensitization of Cannabinoid-Mediated Presynaptic Inhibition of Neurotransmission Between Rat Hippocampal Neurons in Culture.
M. Kouznetsova, B. Kelley, M. Shen, and S. A. Thayer (2002)
Mol. Pharmacol. 61, 477-485
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Internalization Determinants of the Parathyroid Hormone Receptor Differentially Regulate beta -Arrestin/Receptor Association.
J.-P. Vilardaga, C. Krasel, S. Chauvin, T. Bambino, M. J. Lohse, and R. A. Nissenson (2002)
J. Biol. Chem. 277, 8121-8129
   Abstract »    Full Text »    PDF »


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